Structural polymorphism and diversifying selection on the pregnancy malaria vaccine candidate VAR2CSA

Bockhorst, Joseph; Lü, Fangli; Janes, Joel H.; Keebler, Jon; Gamain, B; Awadalla, Philip; Su, Xin-zhuan; Samudrala, Ram; Jojić, Nebojša; Smith, Joseph D.

doi:10.1016/j.molbiopara.2007.06.007

Cited by 111 publications

(182 citation statements)

References 40 publications

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“…Evidence suggests that VAR2CSA is the main target of this protective immunity (9). This, and the fact that VAR2CSA is unusually well conserved (16), suggests that it is possible to obtain a VAR2CSA-based vaccine against PM.…”

mentioning

confidence: 98%

Structural and Functional Insight into How the Plasmodium falciparum VAR2CSA Protein Mediates Binding to Chondroitin Sulfate A in Placental Malaria

Clausen

Christoffersen

Dahlbäck

et al. 2012

Journal of Biological Chemistry

157

202

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mentioning

confidence: 98%

Structural and Functional Insight into How the Plasmodium falciparum VAR2CSA Protein Mediates Binding to Chondroitin Sulfate A in Placental Malaria

Clausen

Christoffersen

Dahlbäck

et al. 2012

Journal of Biological Chemistry

157

202

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“…The identification of groups of PfEMP1s [45] associated with specific disease syndromes is a significant step forward. But are these molecules suited for inclusion in a vaccine?…”

Section: Identifying Conserved Receptor-binding Surfaces On Pfemp1smentioning

confidence: 99%

“…However, VAR2CSA is not a classical PfEMP1 as it lies outside the normal organization of the protein family and is encoded by a single, relatively conserved gene in each parasite genome [26,27,45]. What about the more classical PfEMP1 family members?…”

Section: Identifying Conserved Receptor-binding Surfaces On Pfemp1smentioning

confidence: 99%

Towards an anti-disease malaria vaccine

Lennartz

Lavstsen

Higgins

2017

Emerging Topics in Life Sciences

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Human infective parasites, such as those that cause malaria, are highly adapted to evade clearance by the immune system. In situations where they must maintain prolonged interactions with molecules of their host, they often use parasite surface protein families. These families are highly diverse to prevent immune recognition, and yet, to promote parasite survival, their members must retain the ability to interact with specific human receptors. One of the best understood of the parasite surface protein families is the PfEMP1 proteins of Plasmodium falciparum. These molecules cause infected erythrocytes to adhere to human receptors found on blood vessel and tissue surfaces. This protects the parasite within from clearance by the spleen and also causes symptoms of severe malaria. The PfEMP1 are exposed to the immune system during infection and are therefore excellent vaccine candidates for use in an approach to prevent severe disease. A key question, however, is whether their extensive diversity precludes them from forming components of the malaria vaccines of the future?

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“…However, one specific PfEMP1 variant, known as var2csa, plays a key role in placental infection [209] and may be a suitable target for a vaccine that helps protect pregnant women from the complications of malaria during pregnancy. Although this single variant has a high level of polymorphism [210], recent studies suggest the extent of antigenic diversity may not be high as there appear to be many shared epitopes that are common to different variants [211,212], and antibodies that cross-react to different variants have been induced by vaccination [213,214] and are acquired through natural exposure [211,215] …”

Section: Vaccine Trials and Antigen Polymorphismmentioning

confidence: 99%